Screening a small library of xanthones for antitumor activity and identification of a hit compound which induces apoptosis

João Barbosa, Raquel T. Lima, Diana Sousa, Ana Sara Gomes, Andreia Palmeira, Hugo Seca, Kantima Choosang, Pannee Pakkong, Hassan Bousbaa, Madalena M. Pinto, Emília Sousa, M. Helena Vasconcelos*, Madalena Pedro

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines derived from solid tumors has not been previously studied. The present work aimed at: (i) screening this small series of compounds from an in-house library, for their in vitro cell growth inhibitory activity in human tumor cell lines derived from solid tumors; and (ii) initiate a study of the effect of the most potent compound on apoptosis. The tumor cell growth inhibitory effect of 27 compounds was first analysed in different human tumor cell lines, allowing the identification of a hit compound, TXA1. Its hydrochloride salt TXA1 HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1 HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1 HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis.

Original languageEnglish
Article number21010081
JournalMolecules
Volume21
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Keywords

  • Antitumor activity screening
  • Apoptosis
  • In vitro cell growth assays
  • Thioxanthones

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